Figure 1. Sequence and structural features of AQP4.

a | The schematic depicts the primary amino acid sequence and membrane topology of aquaporin 4 (AQP4). This AQP has eight membrane-embedded helical segments, which are labelled M1–M8, and two translation initiation sites — Met1 and Met23 (black) — corresponding to the two AQP4 isoforms, M1 and M23, respectively. AQP4 tetramers can form orthogonal arrays of particles (OAPs) through intermolecular N-terminal associations between M23 isoforms involving the residues highlighted in purple. The residues in green prevent N-terminal associations between M1 AQP4 molecules. Cysteine residues (in blue) are sites of palmitoylation, and are involved in regulating OAP assembly. The C terminus of AQP4 contains a PDZ domain (in green) that may be involved in protein–protein interactions. b | X-ray crystal structure of human AQP4 (RCSB Protein Data Bank ID: 3GD8) shows the eight membrane-embedded helical segments. c | Freeze-fracture electron micrograph (FFEM) of M23-AQP4-expressing Chinese hamster ovary cells shows that AQP4 OAPs are supermolecular assemblies that have a cobblestone-like array structure (left panel)¹⁴. The middle panel shows a super-resolution micrograph, which was obtained by direct stochastic optical reconstruction microscopy (dSTORM), of cells co-expressing a green fluorescent variant of M23-AQP4 and a red fluorescent variant of M1-AQP4 (REF. 18). From such micrographs, it has been determined that OAPs have a M23-AQP4-enriched core, with M1-AQP4 being found in the periphery of these structures (diagrammatically depicted in the inset on the right). The left panel of part c is reproduced, with permission, from REF. 14 © (1996) American Society for Biochemistry and Molecular Biology. The middle and right panels in part c are modified, with permission, from REF. 18 © (2012) The Company of Biologists Ltd.